ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistancemechanisms to HIV-1 associated with cytidine kinase deficiency

Authors
Groschel, B Himmel, N Cinatl, J Perigaud, C Gosselin, G Imbach, JL Doerr, HW Cinatl, J
Citation
B. Groschel et al., ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistancemechanisms to HIV-1 associated with cytidine kinase deficiency, NUCLEOS NUC, 18(4-5), 1999, pp. 921-926
Citations number
14
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEOSIDES & NUCLEOTIDES
ISSN journal
07328311 → ACNP
Volume
18
Issue
4-5
Year of publication
1999
Pages
921 - 926
Database
ISI
SICI code
0732-8311(1999)18:4-5<921:DA3MPO>2.0.ZU;2-V
Abstract
A 2',3'-dideoxycytidine (ddC)-resistant T-lymphoid eel line (MOLT-4/8(r)ddC (250)), in which deoxycytidine kinase (dCK) gene-expression was decreased w hen compared with parental cells, has been selected. Cytotoxic and antiretr oviral activity of ddC and 3TC was significantly lower in MOLT-4/8(r)ddC(25 0) than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable bo th cytotoxic and antiretroviral activity in parental and ddC-resistant cell s.